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Sean Agbor-Enoh, Joshua L Chan, Avneesh Singh, Ilker Tunc, Sasha Gorham, Jun Zhu, Mehdi Pirooznia, Philip C Corcoran, Marvin L Thomas, Billeta G T Lewis, Moon Kyoo Jang, David L Ayares, Keith A Horvath, Muhammad M Mohiuddin, Hannah Valantine
BACKGROUND: Observational studies suggest that cell-free DNA (cfDNA) is a biomarker of tissue injury in a range of conditions including organ transplantation. However, the lack of model systems to study cfDNA and its relevance to tissue injury has limited the advancements in this field. We hypothesized that the predictable course of acute humoral xenograft rejection (AHXR) in organ transplants from genetically engineered donors provides an ideal system for assessing circulating cfDNA as a marker of tissue injury...
April 26, 2018: Journal of Heart and Lung Transplantation
Miguel R Ossandon, Lokesh Agrawal, Eric J Bernhard, Barbara A Conley, Sumana M Dey, Rao L Divi, Ping Guan, Tracy G Lively, Tawnya C McKee, Brian S Sorg, James V Tricoli
The importance of circulating free DNA (cfDNA) in cancer clinical research was recognized in 1994 when a mutated RAS gene fragment was detected in a patient's blood sample. Up to 1% of the total circulating DNA in patients with cancer is circulating tumor DNA (ctDNA) that originates from tumor cells. As ctDNA is rapidly cleared from the blood stream and can be obtained by minimally invasive methods, it can be used as a dynamic cancer biomarker for cancer early detection, diagnosis, and treatment monitoring...
June 20, 2018: Journal of the National Cancer Institute
G Le Conte, A Letourneau, J Jani, P Kleinfinger, L Lohmann, J-M Costa, A Benachi
OBJECTIVES: To evaluate the performance of noninvasive prenatal testing by cell-free circulating fetal DNA in maternal blood (cfDNA) in screening for trisomies 21 in twin pregnancies. METHODS: CfDNA was performed in 492 patients with twin pregnancies without ultrasound anomalies in the first trimester as a first-line screening test or after serum screening. Data were collected prospectively and a retrospective analysis was done. CfDNA was executed by massive parallel technique...
June 18, 2018: Gynecologie, Obstetrique, Fertilite & Senologie
Ye-Qing Qian, Xiao-Qing Wang, Min Chen, Yu-Qin Luo, Kai Yan, Yan-Mei Yang, Bei Liu, Li-Ya Wang, Ying-Zhi Huang, Hong-Ge Li, Hang-Yi Pan, Fan Jin, Min-Yue Dong
BACKGROUND: Fetal chromosome aberrations and sub-chromosomal copy number variations (CNVs) are not rare. There are several ways to detect duplications and deletions; cell-free DNA screening (cfDNA screening) is nowadays an accurate and safe detection method. The objective of this study is to report the feasibility of cfDNA screening as an indicator of parental balanced chromosome translocation. RESULTS: From February 2015 to March 2016, cfDNA screening was offered to 11344 pregnant women...
June 18, 2018: European Journal of Medical Genetics
Maite Mendioroz, Leyre Martínez-Merino, Idoia Blanco-Luquin, Amaya Urdánoz, Miren Roldán, Ivonne Jericó
Noninvasive tests to diagnose and monitor the progression of neurodegenerative disorders have been a challenge for decades. The aim of this study was to explore the feasibility of applying liquid biopsy procedures to patients with a neurodegenerative disease such as amyotrophic lateral sclerosis (ALS). We isolated plasma cell-free DNA (cfDNA) in 20 ALS patients and 20 controls and used cfDNA to identify a novel differentially methylated mark in RHBDF2 gene in ALS patients compared to controls. Our findings support the notion that liquid biopsy may be applied to living patients as a source of potential epigenetic biomarkers for neurodegenerative disorders...
June 2018: Annals of Clinical and Translational Neurology
Yoshiteru Noda, Takema Kato, Asuka Kato, Haruki Nishizawa, Jun Miyazaki, Mayuko Ito, Sumire Terasawa, Takao Sekiya, Takuma Fujii, Hiroki Kurahashi
Examination of maternal plasma cell free DNA (cfDNA) for noninvasive prenatal testing for fetal trisomy is a highly effective method for pregnant women at high risk. This can be also applied to fetal gender determination in female carriers of severe X-linked disease. PCR analysis is a relatively simpler and less expensive method of detecting Y chromosome-specific repeats (Y-specific PCR; YSP), but is limited by the risk of false-negative results. To address this, we have developed a combined strategy incorporating YSP and an estimation of the fetal DNA fraction...
June 21, 2018: Congenital Anomalies
Philip Burnham, Darshana Dadhania, Michael Heyang, Fanny Chen, Lars F Westblade, Manikkam Suthanthiran, John Richard Lee, Iwijn De Vlaminck
Urinary tract infections are one of the most common infections in humans. Here we tested the utility of urinary cell-free DNA (cfDNA) to comprehensively monitor host and pathogen dynamics in bacterial and viral urinary tract infections. We isolated cfDNA from 141 urine samples from a cohort of 82 kidney transplant recipients and performed next-generation sequencing. We found that urinary cfDNA is highly informative about bacterial and viral composition of the microbiome, antimicrobial susceptibility, bacterial growth dynamics, kidney allograft injury, and host response to infection...
June 20, 2018: Nature Communications
Roni Lehmann-Werman, Judith Magenheim, Joshua Moss, Daniel Neiman, Ofri Abraham, Sheina Piyanzin, Hai Zemmour, Ilana Fox, Talya Dor, Markus Grompe, Giora Landesberg, Bao-Li Loza, Abraham Shaked, Kim Olthoff, Benjamin Glaser, Ruth Shemer, Yuval Dor
Liver damage is typically inferred from serum measurements of cytoplasmic liver enzymes. DNA molecules released from dying hepatocytes are an alternative biomarker, unexplored so far, potentially allowing for quantitative assessment of liver cell death. Here we describe a method for detecting acute hepatocyte death, based on quantification of circulating, cell-free DNA (cfDNA) fragments carrying hepatocyte-specific methylation patterns. We identified 3 genomic loci that are unmethylated specifically in hepatocytes, and used bisulfite conversion, PCR, and massively parallel sequencing to quantify the concentration of hepatocyte-derived DNA in mixed samples...
June 21, 2018: JCI Insight
Elisa Bevilacqua, Serena Resta, Andrew Carlin, Xin Kang, Teresa Cos Sanchez, Jérôme de Marchin, Jacques C Jani
Roche's Ariosa HarmonyTM Prenatal Test, a noninvasive cfDNA (cell-free DNA) method for major trisomies has been available since January-2013 at the authors unit and tests were sent to California. From July-2017 onwards, prenatal cfDNA has been reimbursed in Belgium for all pregnancies, however since then samples are sent to a local technology transfer center. Little data are available on patient's profile and choices towards cfDNA and on the performance of local technology transfer centers. Areas covered: The profiles and choices of women regarding this test were evaluated...
June 18, 2018: Expert Review of Molecular Diagnostics
Xisi Wang, Lijun Wang, Yan Su, Zhixia Yue, Tianyu Xing, Wen Zhao, Qian Zhao, Chao Duan, Cheng Huang, Dawei Zhang, Mei Jin, Xianfeng Cheng, Shenglan Chen, Yi Liu, Xiaoli Ma
To evaluate plasma cell-free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy-nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow-up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR)...
June 14, 2018: Cancer Medicine
Karin Huijsdens-van Amsterdam, Lieve Page-Christiaens, Nicola Flowers, Michael D Bonifacio, Katie M Battese Ellis, Ida Vogel, Else Marie Vestergaard, Javier Miguelez, Mario Henrique Burlacchini de Carvalho, Erik A Sistermans, Mark D Pertile
False-negative cell-free DNA (cfDNA) screening results involving Down syndrome are rare, but have high clinical impact on patients and their healthcare providers. Understanding the biology behind these results may allow for improved diagnostic follow-up and counseling. In 5 different centers offering cfDNA prenatal screening, 9 false-negative results were documented in 646 confirmed cases of trisomy 21; a false-negative rate of 1.4% (95% CI, 0.7-2.6). False-negative results included 4 cases of classical trisomy 21 and 5 cases with a de novo 21q;21q rearrangement...
June 13, 2018: European Journal of Human Genetics: EJHG
Elisa Bevilacqua, Jacques C Jani, Alexandra Letourneau, Silvia F Duiella, Pascale Kleinfinger, Laurence Lohmann, Serena Resta, Teresa Cos Sanchez, Jean-François Fils, Marilyn Mirra, Alexandra Benachi, Jean-Marc Costa
OBJECTIVES: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing, mainly in terms of detection rates for trisomy 21, performed by 2 laboratories using different analytical methods. METHODS: cfDNA testing was performed on 2,870 pregnancies with the HarmonyTM Prenatal Test using the targeted digital analysis of selected regions (DANSR) method, and on 2,635 pregnancies with the "Cerba test" using the genome-wide massively parallel sequencing (GW-MPS) method, with available outcomes...
June 13, 2018: Fetal Diagnosis and Therapy
Veronica C Devall, Robert Goggs, Christina Hansen, Christopher W Frye, Jo-Annie Letendre, Joseph J Wakshlag
OBJECTIVE: To evaluate whether cell-free DNA (cfDNA) concentrations are increased in dogs with exertional rhabdomyolysis and whether concentrations are correlated with serum myoglobin concentration and creatine kinase activity. DESIGN: Observational cohort study. SETTING: Yukon Quest 1,000-mile International Sled Dog Race 2015. ANIMALS: Twelve normal competitive sled dogs; 5 dogs with rhabdomyolysis. INTERVENTIONS: None...
June 13, 2018: Journal of Veterinary Emergency and Critical Care
Marzena Garley, Dorota Dziemiańczyk-Pakieła, Kamil Grubczak, Arkadiusz Surażyński, Dorota Dąbrowska, Wioletta Ratajczak-Wrona, Jolanta Sawicka-Powierza, Jan Borys, Marcin Moniuszko, Jerzy A Pałka, Ewa Jabłońska
Taking into account the previously reported relationship between inflammation and carcinogenesis, and the scant amount of data concerning the role of neutrophil extracellular traps (NETs) in carcinogenesis, we decided to study the process of extracellular trap formation in patients with inflammation as well as in patients with cancer occurring in the same location. For preliminary isolation of neutrophils (PMNs), we used Polymorphprep™, then sorted with Microbeads. The cells were recorded in the incubation chamber with a BD Pathway 855 microscope system...
2018: Journal of Cancer
Parisa Rokni, Afsaneh Mojtabanezhad Shariatpanahi, Ebrahim Sakhinia, Mohammad Amin Kerachian
Detecting cfDNA in plasma or serum could serve as a 'liquid biopsy', for circulating tumor DNA with aberrant methylation patterns offer a possible method for early detection of several cancers which could avoid the need for tumor tissue biopsies. Bone Morphogenetic Protein 3 (BMP3) was identified as a candidate tumor suppressor gene putatively down-regulated in colorectal cancer (CRC). In this study, we aimed to assess the potential role of BMP3 promoter methylation changes in plasma DNA for detection of colorectal cancerous and precancerous lesions...
April 2018: Genes & Genomics
Jingjing Jiao, Gordon P Watt, Heather L Stevenson, Tiffany L Calderone, Susan P Fisher-Hoch, Yuanqing Ye, Xifeng Wu, John M Vierling, Laura Beretta
Telomerase reverse transcriptase ( TERT ) mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether TERT mutations can be detected in circulating cell-free DNA (cfDNA) of patients with HCC and/or cirrhosis and characterize clinical parameters associated with these mutations. We retrieved data on TERT C228T and C250T promoter mutations in 196 HCCs from The Cancer Genome Atlas. We measured these TERT mutations in plasma cfDNA in 218 patients with HCC and 81 patients with cirrhosis without imaging evidence of HCC...
June 2018: Hepatology Communications
Sumera Rizvi, John Eaton, Ju Dong Yang, Vinay Chandrasekhara, Gregory J Gores
The diagnosis of malignant biliary strictures remains problematic, especially in the perihilar region and in primary sclerosing cholangitis (PSC). Conventional cytology obtained during endoscopic retrograde cholangiography (ERC)-guided brushings of biliary strictures is suboptimal due to limited sensitivity, albeit it remains the gold standard with a high specificity. Emerging technologies are being developed and validated to address this pressing unmet patient need. Such technologies include enhanced visualization of the biliary tree by cholangioscopy, intraductal ultrasound, and confocal laser endomicroscopy...
May 2018: Seminars in Liver Disease
Kiersten Rule, Renee J Chosed, T Arthur Chang, J David Wininger, William E Roudebush
PURPOSE: Cell-free DNA (cfDNA) which is present in the blastocoel cavity of embryos is believed to result from physiological apoptosis during development. This study assessed cfDNA content and caspase-3 protease activity in day-5 IVF blastocysts to determine if there was a correlation with embryo morphology. METHODS: Day-5 IVF blastocysts were scored according to the Gardner and Schoolcraft system (modified to generate a numerical value) and cfDNA was collected following laser-induced blastocoel collapsing prior to cryopreservation in 25 μL of media...
June 4, 2018: Journal of Assisted Reproduction and Genetics
Shirin Akter, Ryo Nakao, Yuhei Imasato, Mohammad Zahangir Alam, Ken Katakura
Parasitic infections are common in stray dogs and accurate knowledge of parasite communities in dogs would provide insight into the epidemiology of parasitic diseases. In this study, we used Illumina sequencing technology to evaluate cell-free DNA (cfDNA) as a marker for screening of parasitic infections in dogs. Plasma samples from 14 stray dogs captured in Bangladesh were used in the experiments. An average of 2.3 million reads was obtained for each sample. BLASTn analysis identified 150 reads with high similarity with parasites from 19 different genera...
May 31, 2018: Genomics
Manish Kohli, Jian Li, Meijun Du, David W Hillman, Scott M Dehm, Winston Tan, Rachel Carlson, Michael B Campion, Liguo Wang, Liewei Wang, Huijuan Zhang, Peng Zhang, Deepak Kilari, Chiang-Ching Huang, Liang Wang
BACKGROUND: The prognostic significance of plasma cell-free DNA (cfDNA) androgen receptor amplification (ARamp) in metastatic castration-resistant prostate cancer (mCRPC) compared with circulating tumor cell (CTC) counts is not known. METHODS: As part of correlative aims of a prospective study in mCRPC, concurrent and serial collections of plasma and CTCs were performed. Specimen collections were performed at baseline after progression on androgen deprivation therapy and then 12 weeks later...
June 1, 2018: Prostate Cancer and Prostatic Diseases
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